[Eosinophilic angiocentric fibrosis: a form of IgG4-related systemic disease?]. / Fibrose angiocentrique à éosinophiles : une manifestation de la maladie systémique liée au IgG4 ?

Eosinophilic angiocentric fibrosis is a rare fibro-inflammatory disorder of unknown etiology with only 40 cases reported in the literature. It primarily affects the sinonasal tract and more rarely the orbit, the larynx and the gums. This benign disorder is characterized by a slowly progressive process mimicking a tumor, with frequent recurrences after surgical excision and cortico-therapy. The typical histology consists of fibro-inflammatory lesion with numerous eosinophils, arranged in a perivascular pattern. As the lesion matures, inflammation becomes less intense and the fibrosis progresses with an onion-skin type perivascular fibrosis. A recent paper suggests that EAF is part of the spectrum of IgG4-related systemic disease. We report a case of orbital EAF in an 86-year-old woman which sustained this hypothesis.

Incidencia de gammopatías monoclonales en pacientes infectados por HIV-1 / Incidence of monoclonal gammopathies in HIV-1 infected patients

Se estudió la incidencia de gammopatías monoclonales (GM) en pacientes infectados por HIV-1 y su posible asociación con neoplasias malignas. Se estudiaron 236 pacientes reactivos a la prueba de detección de anticuerpos anti-HVI-1, siguiendo con los criterios para el diagnóstico clínico y serológico propuestos por el CDC (Atlanta). Se observó GM en 24 casos (10,2%). Se clasificaron en GM de baja conc.: menor de 1 g/dl de suero (92%); de mediana conc.: entre 1-2 g/dl (0,4%) y de elevada conc.: mayor de 2 g/dl (0,4%). Los isotipos de las cadenas pesadas fueron identificados como IgG (94,5%) e IgM (5,5%). Del total de pacientes, en seis se diagnosticó Sarcoma de Kaposi y de éstos dos presentaron GM. Las GM que se describen en este trabajo deberían considerarse de significado incierto. Su hallazgo, la identificación, la purificación y el estudio de la actividad de anticuerpos de las mismas, serían de utilidad para dilucidar aspectos de la fisiopatología de este síndrome y para la mejor comprensión de procesos neoplásicos malignos asociados

[Primary myelodysplastic syndrome. Prognostic factors and frequent appearance of monoclonal and polyclonal gammopathies]. / Primäres myelodysplastisches Syndrom. Prognostische Faktoren und gehäuftes Auftreten monoklonaler und polyklonaler Gammopathien.

Prognostic factors were obtained by retrospective analysis of data on 44 patients (34 men and ten women; average age 64 +/- 13 years) with a primary myelodysplastic syndrome. The most important factors for a poor prognosis were the presence of more than 5% blast cells in the bone marrow (P = 0.001), serum platelet count of less than 150,000/microliters (P = 0.05), serum white cell count less than 3000/microliters (not significant) and serum lactate dehydrogenase concentration greater than 240 U/l (P = 0.05). Protein electrophoresis revealed a polyclonal hypergammaglobulinaemia in 15 of 38 patients; in eight of 17 patients with partly normal curve pattern at protein electrophoresis, a monoclonal gammopathy was demonstrated (monoclonal gradient 3.5 g/dl) by immunoelectrophoresis or immunofixation. No prognostic significance could be established for these gammopathies.

Monoclonal gammopathy and multiple myeloma in the elderly.

The term 'benign monoclonal gammopathy' indicates the presence of a monoclonal protein in persons without evidence of multiple myeloma, macroglobulinaemia, amyloidosis, lymphoproliferative disease, or other related disorders. The term 'monoclonal gammopathy of undetermined significance' (MGUS) is preferable because it is not known at diagnosis whether an M-protein will remain stable and benign or develop into symptomatic multiple myeloma or related disorders. Immunoelectrophoresis and immunofixation of the serum and urine are necessary to determine the presence and type of M-protein. At the Mayo Clinic, follow-up data have been gathered for more than 13 years on 241 patients with an initial benign monoclonal gammopathy. Nineteen per cent of these patients developed multiple myeloma, macroglobulinaemia, amyloidosis, or related diseases during the follow-up period. There is no reliable technique for differentiating a patient with a benign monoclonal gammopathy from one who will subsequently develop a serious disease. It is necessary to follow these patients indefinitely. Important in the complete understanding of the elderly patient with monoclonal gammopathy are the following: clinical manifestations, laboratory findings, and differential diagnosis of multiple myeloma; the course and prognosis and the induction therapy and treatment of multiple myeloma; newer therapeutic approaches; and the management of complications such as hypercalcaemia, hyperuricaemia, renal failure, bacterial infections, skeletal disease, and neurological problems.

Application of the immunoperoxidase technic to bone marrow trephine biopsies in the classification of patients with monoclonal gammopathies.

This study evaluated the utility of the immunoperoxidase method as applied to bone marrow sections in the diagnosis of patients with monoclonal gammopathies. Intracellular immunoglobulin light chains were identified in fixed, decalcified bone marrow biopsy sections from 66 patients with monoclonal proteins, using an avidin-biotin-peroxidase complex immunoperoxidase method. In all cases the predominant light chain identified in the bone marrow biopsy correlated with the monoclonal light chain identified in the serum. In addition, a light chain ratio was defined that correlated with the clinical diagnoses. The light chain ratios were highest in patients with multiple myeloma and were significantly different from those with monoclonal gammopathy of undetermined significance. There was no correlation between level of serum monoclonal protein and light chain ratios. The ratios were also high in patients with macroglobulinemia, primary amyloidosis, and renal disease secondary to monoclonal proteins but without overt myeloma. Determination of light chain ratios differentiated patients with multiple myeloma from those with monoclonal gammopathy of undetermined significance and helped identify patients with end organ damage secondary to monoclonal proteins but without overt myeloma.

Prognostic relevance of cellular morphology in multiple myeloma.

Morphological characteristics of tumor cells have been employed in the prognosis of lymphomas and solid tumors. This report documents an attempt to predict survival from the known cytologic heterogeneity in multiple myeloma. Myeloma cells in bone marrow smears from patients at diagnosis were evaluated by assigning them to morphologically defined categories. Cox's multivariate regression model for censored survival data was used to generate optimal weights, which served as coefficients in two regression equations to estimate death risk from cellular morphology. Step-wise procedures excluded redundant parameters. "Myeloma morphology score" (MMS) discriminates significantly (p less than 0.0001) among 3 stages, with median survival times of 42.5, 30.7, and 9.1 mo. For clinical routine application, "myeloma progression score" (MPS), the weight sum of the proportion of plasmablasts and the extent of bone marrow plasma cell infiltration, is suggested as a simple prognostic tool. Its discriminative power is very high [p less than 10(-9)]. Median survival times of greater than 71.5, 23.4, and 6.1 mo were found for good, moderate, and poor risk groups, respectively. However, staging is not confined to three subgroups, grouping is flexible, and pairs of data can be matched. This fact may prove to be valuable in designing prognosis-controlled clinical trials or theoretical studies on cellular differentiation. Preliminary results suggest changes in morphology due to disease progression and/or the effect of therapy on tumor kinetics. Most importantly, staging according to MPS or MMS may facilitate the adaption of therapy to the current state of the disease in patients with multiple myeloma.

[Critical review of 243 monoclonal immunoglobulinopathies]. / Revue critique de 243 immunoglobulinopathies monoclonales.

243 cases of monoclonal immunoglobulinopathy were seen at the CHR in Rennes over a period of three years. The authors studied successively the relationship between the monoclonal immunoglobulin and the clinical diagnosis the distribution of the monoclonal compounds according to the heavy chain class and the identification of the light chains, the distribution of the immunoglobulinopathies in terms of the age and the sex of the patients and the correlation between the clinical diagnosis and various laboratory findings (proteins concentration, concentration of normal immunoglobulins, sedimentation rate...). The results obtained are in line with the principal data in the literature concerning monoclonal immunoglobulinopathies. However, the authors demonstrated, in the studied population, a higher percentage of monoclonal IgM than is usually reported. Furthermore, these IgM immunoglobulins, present in Waldenstrom's disease and frequently seen in various other immunoglobulinopathies, were essentially found in men.

"Secondary" plasma-cell dyscrasia: a plea for change in terminology, with an illustrative case report.

The demonstration of monoclonal, homogeneous immunoglobulin or its subunit is the hallmark of plasma-cell dyscrasia. Plasma-cell dyscrasia can be classified into two main groups: "primary" and "secondary". The increasing use of protein electrophoresis and immunoelectrophoresis has contributed to the increased frequency of secondary monoclonal gammopathy and to the better recognition of its clinical significance. Secondary monoclonal gammopathy usually stems from the reactive unbalanced proliferation of B cells resulting from chronic inflammatory diseases or from other malignancies. Only in some cases its cause is difficult to assert. A case of secondary plasma-cell dyscrasia of undetermined cause is presented. The patient had IgG kappa monoclonal gammopathy of 3580 mg/dl, and multiple osteolytic bone lesions. However the histopathological picture showed a chronic inflammatory process, and the diagnosis of multiple myeloma could not be established. The diagnostic problems in this case are discussed, with the recommendation that more strict and accurate immunochemical terms concerning monoclonal gammopathy be used.

[Immunoglobulins and dysglobulinemias. Introduction and general data]. / Immunoglobulines et dysglobulinémies. Introduction et données générales

The author reviews the present state of knowledge of value in rheumatology concerning serum immunoglobulins, their structure, their cellular biosynthesis, and their relation to membrane immunoglobulins of the B lymphocytes. He then examines the concept of dysglobulinaemia and explains why the terms monoclonal immunoglobulin and monoclonal immunoglobulinopathy are preferable to dysglobulinaemia and paraprotein. The clinical and immunochemical classification of monoclonal immunoglobulins, the problem of amylosis, and the relationship with plasmocytic dyscrasias and with the cryoglobulins are then discussed. Afterwards the pathogeny of these affections is briefly considered.